BRITISH MEDICAL JOURNAL
153
20 JANUARY 1979
Characteristics affecting fibrinolytic activity and plasma fibrinogen concentrations T W MEADE, R CHAKRABARTI, A P HAINES, W R S NORTH, YVONNE STIRLING British Medical Journal, 1979, 1, 153-156
Summary and conclusions As part of a study to determine the extent to which the haemostatic system is implicated in the onset of clinically manifest ischaemic heart disease, characteristics influencing fibrinolytic activity (FA) and plasma fibrinogen concentrations were examined in 1601 men aged 18-64 and 707 women aged 18-59 in several occupational groups in North-west London. In men FA noticeably decreased till the age of about 58, when there was a small rise. In women a small increase in FA between 18 and about 40 was followed by a slightly larger fall between 40 and 59. There was a pronounced negative association of FA with obesity. FA was significantly less in smokers than non-smokers, though the effect was not large. FA increased with alcohol consumption. FA in men appeared to be greatest in the lower social classes, and men on night shift had poorer FA than those on day work. FA was greater in women using oral contraceptives than in those not using these preparations. In both sexes FA increased with exercise, but there were no associations between any of the characteristics studied and the increase. Plasma fibrinogen concentrations increase with age and obesity, are higher in smokers than non-smokers, and fall with alcohol consumption. In women the concentrations are higher in those using oral contraceptives. The general epidemiology of FA and plasma fibrinogen concentrations suggests that they may well be implicated in the pathogenesis of ischaemic heart disease. Introduction Clinical observations suggest that poor fibrinolytic activity (FA)1 2and high plasma fibrinogen concentrations3 4 may be implicated in the onset and course of thromboembolic disease. Epidemiological evidence, however, is scarce. Prospective data on associations of FA and fibrinogen concentrations with ischaemic heart disease (IHD) will eventually be available from the Northwick Park Heart Study (NPHS).' Meanwhile crosssectional data at recruitment to the study provide an opportunity for seeing whether the general epidemiology of FA and fibrinogen concentrations is consistent with their having a role in the pathogenesis of IHD. If these variables are influenced by personal and environmental factors-such as age, smoking, and obesity-already known to be associated with an increased risk of the disease the case for such a role would be strengthened. In turn there would be added reason to consider the contribution to IHD of thrombogenic mechanisms as well as those concerned
with lipids and blood pressure. We therefore describe several personal and environmental characteristics influencing FA and plasma fibrinogen concentrations in participants in the study.
Study population and methods Full details of the population being studied and methods used have been reported.5 The population consists of members of several occupational groups in North-west London. This report deals with only white participants-namely, 1601 men aged 18-64 and 707 women (88 users of oral contraceptives) aged 18-59. FA is expressed as 100/dilute clot lysis time6 in hours. Thrombin-"clottable" fibrinogen is measured gravimetrically'; it is log-normally distributed,5 and all mean values given here are geometric. Blood for measurement of FA is taken before and after a spell of exercise consisting in stepping on and off a chair 20 times (except in those with clinical or electrocardiographic manifestations of IHD, who are not exercised, and from whom only the pre-exercise sample is available). Pulse rates are recorded before and after exercise. Fibrinogen concentrations are determined in the pre-exercise sample. All samples are taken between 0700 and 1100. The personal and environmental characteristics considered here are age, sex, smoking habit, alcohol consumption, social class, obesity, current use or otherwise of oral contraceptives in premenopausal women, and, in men, working shift (day or night). Because many of the characteristics studied are associated with one another-for example, smoking and social class-step-wise multiple regression has been used to indicate the independent contribution of each characteristic to FA and fibrinogen concentration; these analyses are based on the number of cigarettes (or pipe or cigar equivalents) smoked and grams of alcohol consumed daily. One cigar or 1 g pipe tobacco is taken as equivalent to one cigarette. Alcohol consumption is elicited at interview in terms of weekly consumption but expressed as daily consumption. The figure and tables I-IV show the results of the regression analysis. In tables I and IV smokers are those smoking at least one cigarette, pipe, or cigar a day. Ex-smokers are included with non-smokers. In table I drinkers are those who recorded a regular weekly intake of alcohol, of whatever amount. Teetotallers and those whose stated intake is at less than weekly intervals are defined as non-drinkers. About 80%o of weekly alcohol consumption (by weight) among male drinkers was in the form of beer. Obesity is assessed from the sum of the skinfold thicknesses at triceps, subscapular, suprailiac, and forearm sites. Numbers of participants in different analyses vary slightly because of missing data.
Fibrinolytic activity Men
W-r,n,,-
* 2020
30
40
50
60
Plasma fibrinogen 41
4 1
Men
3
MRC-DHSS Epidemiology and Medical Care Unit, Northwick Park Hospital, Harrow, Middlesex HAl 3UJ T W MEADE, BM, MRCP, director R CHAKRABARTI, MB, MRCPATH, member of scientific staff A P HAINES, MB, MRCP, member of scientific staff W R S NORTH, MA, MSC, member of scientific staff YVONNE STIRLING, FIMLS, head technician
0
301
3
20 30 Age
40
50
60 65
Women
H_
,a-°< 0
20 30 40 50 60 Age Mean fibrinolytic activities and plasma fibrinogen concentrations before ( o ) and after (*) exercise in men and women at various ages. (Minimum numbers in any five-year age group: men 87, women 42.)
154
BRITISH MEDICAL JOURNAL
20 JANUARY 1979
Results
TABLE IV-Mean fibrinolytic activities (100/lysis time) in premenopausa women by smoking 'habit and oral contraceptive use. (Numbers of women in
The following simplified regression equations indicate the independent contributions of the various characteristics to FA and fibrinogen concentration. Figures in square brackets are t values associated with the regression coefficients.
parentheses)
Men: FA (pre-exercise)=28-4+0-006 [6-19] x (age-58)2 -0-1[3-28] x cigarettes+0- 07 [4-31] x alcohol-0 2 [10-72] x skinfolds+ 10 [3-67] x social class-4 [3 93] x shift + RSD, 14-0 Fibrinogen= 1-72+0-02 [16-64] x age+0 01 [6 64] x cigarettes-0-002 [2 82] x alcohol+ 0005 [5-17] x skinfolds±RSD, 0-62 Women: FA (pre-exercise)=39-2-0 01 [2-98] x (age-39)2 0-2 [3 34] x cigarettes-0-16 [6-13] x skinfolds+6 [3-58] x oral contraceptive use ± RSD, 14-1 Fibrinogen =2.33+0 0005 [8-46] x (age-23)2+0-006 [2 24] x cigarettes-0-015 [3-81] x alcohol+0-006 [5-68] x skinfolds+0 24 [3 23] x oral contraceptive use ±RSD, 0-59 where age =age in years; cigarettes =number of cigarettes (or equivalents)/day; alcohol =g/day, stated intake; skinfolds =sum of skinfold thicknesses at four sites (mm); social class= 1-6 (for I, II, III, non-manual, III manual, IV, V); oral contraceptive use=0 (no), 1 (yes); shift=0 (day men), 1 (night men); and RSD =residual standard deviation.
Where t>1 94, P2 57, P3-34, P
153
20 JANUARY 1979
Characteristics affecting fibrinolytic activity and plasma fibrinogen concentrations T W MEADE, R CHAKRABARTI, A P HAINES, W R S NORTH, YVONNE STIRLING British Medical Journal, 1979, 1, 153-156
Summary and conclusions As part of a study to determine the extent to which the haemostatic system is implicated in the onset of clinically manifest ischaemic heart disease, characteristics influencing fibrinolytic activity (FA) and plasma fibrinogen concentrations were examined in 1601 men aged 18-64 and 707 women aged 18-59 in several occupational groups in North-west London. In men FA noticeably decreased till the age of about 58, when there was a small rise. In women a small increase in FA between 18 and about 40 was followed by a slightly larger fall between 40 and 59. There was a pronounced negative association of FA with obesity. FA was significantly less in smokers than non-smokers, though the effect was not large. FA increased with alcohol consumption. FA in men appeared to be greatest in the lower social classes, and men on night shift had poorer FA than those on day work. FA was greater in women using oral contraceptives than in those not using these preparations. In both sexes FA increased with exercise, but there were no associations between any of the characteristics studied and the increase. Plasma fibrinogen concentrations increase with age and obesity, are higher in smokers than non-smokers, and fall with alcohol consumption. In women the concentrations are higher in those using oral contraceptives. The general epidemiology of FA and plasma fibrinogen concentrations suggests that they may well be implicated in the pathogenesis of ischaemic heart disease. Introduction Clinical observations suggest that poor fibrinolytic activity (FA)1 2and high plasma fibrinogen concentrations3 4 may be implicated in the onset and course of thromboembolic disease. Epidemiological evidence, however, is scarce. Prospective data on associations of FA and fibrinogen concentrations with ischaemic heart disease (IHD) will eventually be available from the Northwick Park Heart Study (NPHS).' Meanwhile crosssectional data at recruitment to the study provide an opportunity for seeing whether the general epidemiology of FA and fibrinogen concentrations is consistent with their having a role in the pathogenesis of IHD. If these variables are influenced by personal and environmental factors-such as age, smoking, and obesity-already known to be associated with an increased risk of the disease the case for such a role would be strengthened. In turn there would be added reason to consider the contribution to IHD of thrombogenic mechanisms as well as those concerned
with lipids and blood pressure. We therefore describe several personal and environmental characteristics influencing FA and plasma fibrinogen concentrations in participants in the study.
Study population and methods Full details of the population being studied and methods used have been reported.5 The population consists of members of several occupational groups in North-west London. This report deals with only white participants-namely, 1601 men aged 18-64 and 707 women (88 users of oral contraceptives) aged 18-59. FA is expressed as 100/dilute clot lysis time6 in hours. Thrombin-"clottable" fibrinogen is measured gravimetrically'; it is log-normally distributed,5 and all mean values given here are geometric. Blood for measurement of FA is taken before and after a spell of exercise consisting in stepping on and off a chair 20 times (except in those with clinical or electrocardiographic manifestations of IHD, who are not exercised, and from whom only the pre-exercise sample is available). Pulse rates are recorded before and after exercise. Fibrinogen concentrations are determined in the pre-exercise sample. All samples are taken between 0700 and 1100. The personal and environmental characteristics considered here are age, sex, smoking habit, alcohol consumption, social class, obesity, current use or otherwise of oral contraceptives in premenopausal women, and, in men, working shift (day or night). Because many of the characteristics studied are associated with one another-for example, smoking and social class-step-wise multiple regression has been used to indicate the independent contribution of each characteristic to FA and fibrinogen concentration; these analyses are based on the number of cigarettes (or pipe or cigar equivalents) smoked and grams of alcohol consumed daily. One cigar or 1 g pipe tobacco is taken as equivalent to one cigarette. Alcohol consumption is elicited at interview in terms of weekly consumption but expressed as daily consumption. The figure and tables I-IV show the results of the regression analysis. In tables I and IV smokers are those smoking at least one cigarette, pipe, or cigar a day. Ex-smokers are included with non-smokers. In table I drinkers are those who recorded a regular weekly intake of alcohol, of whatever amount. Teetotallers and those whose stated intake is at less than weekly intervals are defined as non-drinkers. About 80%o of weekly alcohol consumption (by weight) among male drinkers was in the form of beer. Obesity is assessed from the sum of the skinfold thicknesses at triceps, subscapular, suprailiac, and forearm sites. Numbers of participants in different analyses vary slightly because of missing data.
Fibrinolytic activity Men
W-r,n,,-
* 2020
30
40
50
60
Plasma fibrinogen 41
4 1
Men
3
MRC-DHSS Epidemiology and Medical Care Unit, Northwick Park Hospital, Harrow, Middlesex HAl 3UJ T W MEADE, BM, MRCP, director R CHAKRABARTI, MB, MRCPATH, member of scientific staff A P HAINES, MB, MRCP, member of scientific staff W R S NORTH, MA, MSC, member of scientific staff YVONNE STIRLING, FIMLS, head technician
0
301
3
20 30 Age
40
50
60 65
Women
H_
,a-°< 0
20 30 40 50 60 Age Mean fibrinolytic activities and plasma fibrinogen concentrations before ( o ) and after (*) exercise in men and women at various ages. (Minimum numbers in any five-year age group: men 87, women 42.)
154
BRITISH MEDICAL JOURNAL
20 JANUARY 1979
Results
TABLE IV-Mean fibrinolytic activities (100/lysis time) in premenopausa women by smoking 'habit and oral contraceptive use. (Numbers of women in
The following simplified regression equations indicate the independent contributions of the various characteristics to FA and fibrinogen concentration. Figures in square brackets are t values associated with the regression coefficients.
parentheses)
Men: FA (pre-exercise)=28-4+0-006 [6-19] x (age-58)2 -0-1[3-28] x cigarettes+0- 07 [4-31] x alcohol-0 2 [10-72] x skinfolds+ 10 [3-67] x social class-4 [3 93] x shift + RSD, 14-0 Fibrinogen= 1-72+0-02 [16-64] x age+0 01 [6 64] x cigarettes-0-002 [2 82] x alcohol+ 0005 [5-17] x skinfolds±RSD, 0-62 Women: FA (pre-exercise)=39-2-0 01 [2-98] x (age-39)2 0-2 [3 34] x cigarettes-0-16 [6-13] x skinfolds+6 [3-58] x oral contraceptive use ± RSD, 14-1 Fibrinogen =2.33+0 0005 [8-46] x (age-23)2+0-006 [2 24] x cigarettes-0-015 [3-81] x alcohol+0-006 [5-68] x skinfolds+0 24 [3 23] x oral contraceptive use ±RSD, 0-59 where age =age in years; cigarettes =number of cigarettes (or equivalents)/day; alcohol =g/day, stated intake; skinfolds =sum of skinfold thicknesses at four sites (mm); social class= 1-6 (for I, II, III, non-manual, III manual, IV, V); oral contraceptive use=0 (no), 1 (yes); shift=0 (day men), 1 (night men); and RSD =residual standard deviation.
Where t>1 94, P2 57, P3-34, P
